Mesoporous platinum (mPt) nanozyme possessed enzyme-like property of catalase (CAT) and peroxidase (POD), but the insufficient hydrogen peroxide (H 2 O 2 ) concentration severely restricted its application in photodynamic therapy (PDT) and catalytic therapy. Herein, by depositing ultrasmall gold nanoparticles (AuNPs) and modifying photosensitizer IR808, a multifunctional nanozyme (mPt@Au-IR808) was designed to promote PDT/catalytic therapy through cascade enzyme-like reactions of glucose oxidase (GOx) and CAT/POD. In tumor microenvironment, the CAT-like oxygen (O 2 ) generation improved the PDT efficacy, and the POD-like hydroxyl radical (·OH) generation achieved endogenous catalytic therapy. Using the GOx/CAT-like activities and endogenous H 2 O 2 , the yields of singlet oxygen and ·OH were significantly promoted. Furthermore, mPt@Au-IR808 showed higher photothermal conversion efficiency (41.2%) than mPt (36.1%). By combining the photothermal therapy and enhanced PDT/catalytic therapy, the developed mPt@Au-IR808 nanozyme showed excellent anti-tumor efficacy, which will be promising as cascade nanozyme to promote photo/catalytic therapy.
Junya Lu,Luming Song,Shuaipeng Feng,Kaili Wang,Yuling Mao,Yikun Gao,Qinfu Zhao,Siling Wang
Nanozyme-mediated tumor catalytic therapy has recently garnered attention as a means of destroying tumor cells and eliciting anti-tumor immune responses. Herein, a copper-doped mesoporous polydopamine (CP) nanozyme modified with triphenylphosphine (TPP) and hyaluronic acid (HA) was designed as a mitochondrial oxidative stress amplifier (CPTH) for inducing apoptosis and promoting immune responses with the assistance of mild photothermal therapy. The density functional theory (DFT) revealed the superoxide dismutase-like reaction mechanism of nanozymes, and combined with 3-amino-1,2,4-triazole (AT, catalase inhibitor) to achieve the goal of increasing the source and reducing the off-target consumption of intra-mitochondrial H 2 O 2 . Meanwhile, CPTH-AT nanozyme was found to amplify mitochondrial oxidative stress by inducing powerful oxidative OH through intra-mitochondrial GSH consumption and exerting peroxidase-like activity. The induction of mitochondrial oxidative damage serves as a trigger for the release of tumor-associated antigens. Thus, CPTH-AT nanozyme combined with mild photothermal therapy caused substantial exposure of damage-associated molecular patterns, maximizing the incidence of tumor immunogenic cell death. Moreover, nanozymes further promoted the dendritic cells maturation and recruitment, increased the infiltration of cytotoxic T lymphocytes and helper T cells, and decreased the proportion of regulatory T cells. In brief, the mitochondria-targeted nanozyme-based biocatalytic immunotherapy combined with mild photothermal therapy represents a promising cancer therapeutic strategy, establishing new paradigms for improving the bio-applications of nanozymes.
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